3-131468049-CA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_007208.4(MRPL3):c.894+41del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.66 (29785 hom., cov: 0)
  • Exomes 𝑓: 0.47 (27967 hom.)
  • Failed GnomAD Quality Control
• Consequence: MRPL3 NM_007208.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.292

Genes affected

MRPL3 (HGNC:10379): (mitochondrial ribosomal protein L3) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein that belongs to the L3P ribosomal protein family. A pseudogene corresponding to this gene is found on chromosome 13q. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 3-131468049-CA-C is Benign according to our data. Variant chr3-131468049-CA-C is described in ClinVar as [Benign]. Clinvar id is 1239761.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRPL3	NM_007208.4	c.894+41del		intron_variant		ENST00000264995.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRPL3	ENST00000264995.8	c.894+41del		intron_variant		1	NM_007208.4	P1
MRPL3	ENST00000425847.6	c.975+41del		intron_variant		2
MRPL3	ENST00000511168.5	c.937+41del		intron_variant		2
MRPL3	ENST00000510043.1	n.318+41del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.658 AC: 90613 AN: 137620 Hom.: 29757 Cov.: 0

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.659

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.653

GnomAD3 exomes AF: 0.516 AC: 58001 AN: 112418 Hom.: 5694 AF XY: 0.509 AC XY: 31626 AN XY: 62146

Gnomad AFR exome AF: 0.692

Gnomad AMR exome AF: 0.506

Gnomad ASJ exome AF: 0.481

Gnomad EAS exome AF: 0.496

Gnomad SAS exome AF: 0.483

Gnomad FIN exome AF: 0.495

Gnomad NFE exome AF: 0.514

Gnomad OTH exome AF: 0.517

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.471 AC: 328236 AN: 697542 Hom.: 27967 Cov.: 0 AF XY: 0.472 AC XY: 169258 AN XY: 358756

Gnomad4 AFR exome AF: 0.615

Gnomad4 AMR exome AF: 0.480

Gnomad4 ASJ exome AF: 0.457

Gnomad4 EAS exome AF: 0.459

Gnomad4 SAS exome AF: 0.442

Gnomad4 FIN exome AF: 0.485

Gnomad4 NFE exome AF: 0.468

Gnomad4 OTH exome AF: 0.475

GnomAD4 genome AF: 0.659 AC: 90662 AN: 137662 Hom.: 29785 Cov.: 0 AF XY: 0.653 AC XY: 43493 AN XY: 66648

Gnomad4 AFR AF: 0.875

Gnomad4 AMR AF: 0.599

Gnomad4 ASJ AF: 0.555

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.652

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs56928817; hg19: chr3-131186893;